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The contribution by Kim and Boukouvala, "Machine learning-based surrogate modeling for data-driven optimization: A comparison of subset selection for regression techniques," presents a comprehensive comparison ...doi:10.1007/s11590-019-01499-6 fatcat:lykk4wr7nbdh5pu4b3udts4tli
Simulation-based optimization is a research area that is currently attracting a lot of attention in many industrial applications, where expensive simulators are used to approximate, design, and optimize real systems. Pharmaceuticals are typical examples of high-cost products which involve expensive processes and raw materials while at the same time must satisfy strict quality regulatory specifications, leading to the formulation of challenging and expensive optimization problems. The maindoi:10.1007/s12247-013-9154-1 fatcat:lyajoe4jfnb4jit6sjg6tg45qy
more »... e of this work was to develop an efficient strategy for simulation-based design and optimization using surrogates for a pharmaceutical tablet manufacturing process. The proposed approach features surrogate-based optimization using kriging response surface modeling combined with black-box feasibility analysis in order to solve constrained and noisy optimization problems in less computational time. The proposed methodology is used to optimize a direct compaction tablet manufacturing process, where the objective is the minimization of the variability of the final product properties while the constraints ensure that process operation and product quality are within the predefined ranges set by the Food and Drug Administration.
We need to design the CCUS network supply chain such that the sources are optimally connected with the utilization and sequestration sites (Hasan, Boukouvala, First, and Floudas, 2014) . ... However, the transportation cost can vary from as low as $0.20 to as high as $40 for each ton of CO 2 , depending on the distance between a source and a utilization/sequestration site (Hasan, Boukouvala ...doi:10.1016/j.compchemeng.2015.04.034 fatcat:zepw42ajtzdofbmi62i546v7bq
of the polytope.2 et al. (1998); Davis and Ierapetritou (2007) ; Caballero and Grossmann (2008) ; Davis and Ierapetritou (2009) ; Quan et al. (2013); Viana et al. (2013); Hasan et al. (2012, 2014); Boukouvala ...doi:10.1016/j.ejor.2015.12.018 fatcat:jwe7b7ivrzhrjbttdl74eff2pe
In this work, a dynamic flowsheet model for the production of pharmaceutical tablets through a continuous wet granulation process is developed. The unit operation models which are integrated to compose the process line form a hybrid configuration which is comprised of a combination of mechanistic models, population balance models, and empirical correlations, based on the currently available process knowledge for each individual component. The main objective of this study is to provide guidancedoi:10.1007/s12247-012-9143-9 fatcat:enlqqfqyxrh7zmu7fbuwkujnwi
more »... n terms of the necessary steps which are required in order to move from the unit operation level to the simulation of an integrated continuous plant operation. Through this approach, not only significant process conditions for each individual process are identified but also crucial interconnecting parameters which affect critical material properties of the processed powder stream are distinguished. Through the integration of the dynamic flowsheet with a final component of tablet dissolution, the connection of the processing history of a set of powders which undergo wet granulation and are contained in each produced tablet to the release rate of the pharmaceutical ingredient is enabled. The developed flowsheet is used for the simulation of different operating scenarios and disturbances which are often encountered during operation for the assessment of their effects towards critical material attributes, product properties, and the operation of further downstream processes. Simulation results demonstrate that granulation and milling which control the particle size distribution of the processed powder mixture highly affect the hardness and dissolution of the produced tablets.
More details on the development of the PBM can be found in Boukouvala et al. (Fani Boukouvala, et al., 2011b ). ... Ramachandran (Fani Boukouvala, et al., 2011a; Poon, et al., 2009; Rohit Ramachandran, et al., 2012a; Rohit Ramachandran & Barton, 2010; Rohit Ramachandran & Chaudhury, 2012b; Rohit Ramachandran, Immanuel ...fatcat:b7hx53bvhza7pgplam4rlpxrqy
Dear Colleagues, It is our pleasure to announce that the following two papers shared the 2017 OPTL Best Paper Award: Fani Boukouvala, Christodoulos A. ...doi:10.1007/s11590-018-1379-y fatcat:svsetvfuxbavxjj5fe4qp6gb2u
Burn injury and infections can lead to an uncontrolled and prolonged action of inflammatory response in the body, which increases the mortality rate of patients. To gain a more comprehensive understanding of these complex physiological changes and to propose therapeutic approaches to combat the deleterious consequences of burn and septic shocks, it is essential to develop animal models exhibiting patho-physiological behaviors similar to those of patients. This was addressed, in this study, by afatcat:mkbp5ldixfbjla3vjnv2a6c25u
more »... systematic analysis of local and systemic responses-including the measurements of inflammatory mediators, gene expression and metabolic profiles of liver-in rat models receiving 20% total body surface area (TBSA) scald burn injury or cecal ligation and puncture (CLP) treatment. All animal groups had 100% survival for at least 10 days following treatments. CLP caused a ~10% weight loss indicating an accelerated breakdown of skeletal muscle iii protein. It was found that a certain number of cytokines and chemokines, such as MCP-1, GROK/KC, IL-12, IL-18, and IL-10, were significantly altered following the treatments including SCLP (control of CLP) which is a sterile surgical treatment where cecum is not ligated and punctured. Gene expression analysis elucidated that hepatic transcriptional response to burn injury was mainly related to pro-inflammatory and anti-inflammatory gene groups and genes involved in lipid biosynthesis and central carbon metabolism. Shortly after the CLP treatment, genes related to Toll like receptors and MAPK signaling pathway were significantly up-regulated. Significant changes in the genes associated with acute phase protein synthesis were also observed following the burn and CLP. Furthermore, perfusion experiments elucidated that hepatic metabolic response to burn injury and sepsis was characterized by an up-regulation of pathways including gluconeogenic reactions (sources of which are mainly lactate, aspartate, glycerol and glutamine), urea production from arginine, and serine-glycine inter-conversion. On the other hand, weight values of these pathways were dramatically decreased following the SCLP treatment. In summary, in this study, bioinformatics tools (clustering and metabolic network analysis algorithms) and animal models of burn and CLP were utilized to understand the various layers of regulation and capture the entire scope and complexity of the inflammatory response. iv ACKNOWLEDGEMENT I wish to express my sincere gratitude to my advisors Prof. Marianthi Ierapetritou, Prof. Ioannis Androulakis, and Prof. Francois Berthiaume for their continuous support, guidance and help throughout this study. I have understood from these worthy individuals that being inquisitive, explorative and hardworking is the most crucial thing for any research endeavor. This approach has further reshaped my outlook on life and for that I am extremely thankful. I would also like to thank to Dr. Jagadeeshan Sunderram for being a member of my thesis committee and for his valuable comments on my research proposal. The financial support from NIH grant GM082974 is gratefully acknowledged. Moreover, I am grateful to my friends
Burn injury leads to a prolonged inflammatory response in the body. Moreover, severe burn injuries are always associated with bacterial infections which cause more persistent inflammatory response, resulting in prolonged hyper-metabolism and hyper-catabolism on systemic level. Despite significant advances in patient care, morbidity and mortality remain high in those patients. The difficulty in developing new and more effective medications is due, in part, to our incomplete understanding of thefatcat:vxlpas2qxnd6jdgdp5fmlro32a
more »... nderlying pathophysiology of the disease. Liver, the main organ regulating both the inflammation and metabolism plays a key role in responding to external injuries. Thus, analyzing the responses in liver to burn, infection and "double hits" injury from global perspective as well as in a timely manner may offer a molecular framework for study on the pathophysiology of systemic inflammation induced by injuries. The overall studies were divided into single injury in which the animals were subjected to single burn injury or single cecal ligation and puncture (CLP) injury individually and "double hits" injury in which the rats were subjected to a burn injury and subsequent CLP injury. Animals were sacrificed at various time points, and whole liver samples were analyzed using Affymetrix Rat iii Genome 230 2.0 Arrays. After identifying differentially expressed probesets in injury rats vs. sham over time, the concatenated data sets corresponding to these differentially expressed probesets in injury and sham were combined and analyzed using a "consensus clustering" approaches. Ingenuity Pathway Analysis (IPA) was used to functionally annotate genes, and RT-PCR was used to confirm microarray trends. Both single burn and CLP injury induces the activation of pro-inflammatory response, anti-inflammatory response, and enhanced synthesis of acute-phase proteins, increased metabolism and tissue damage. Genes which are directly in response to bacteria removal are only triggered in CLP injury. In double hits study, burn priming prior to CLP disrupts the transcriptional response in the liver to septic injury in the rat by altering the onset of anti-bacterial functions in the liver. In addition, burn enhanced hyper metabolic conditions through aggressive amino acid degradation at critical time points. iv ACKNOWLEDGEMENT This dissertation would not have been possible without the guidance and the help of several individuals who in one way or another contributed and extended their valuable assistance in the preparation and completion of this study. First and foremost I provide my sincerest gratitude to my supervisor, Prof. Ioannis P. Androulakis, who has supported me throughout my 5 years research with his patience and knowledge whilst allowing me the room to work in my own way. I attribute the level of my Doctorate degree to his encouragement and effort and without him this thesis, too, would not have been completed or written. One simply could not wish for a better or friendlier supervisor. Then I wish to express my sincere gratitude to my thesis committee member, Prof. Francois Berthiaume, Prof. Marianthi Ierapetritou and Prof. Li Cai for their continuous support, guidance and help throughout this study. I have understood from these worthy individuals that being inquisitive, explorative and hardworking is the most crucial thing for any research endeavor. The financial support from NIH grant GM082974 is gratefully acknowledged. Moreover, I am grateful to my friends
Optimization using both models and input-output data Fani Boukouvala (Georgia Institute of Technology -Atlanta, US) License Creative Commons BY 3.0 Unported license © Fani Boukouvala Joint work of Fani ... Boukouvala, Jianyuan Zhai, Sun Hye Kim In many engineering fields, there is a continuously increasing interest in coupling equationbased first-principle modeling with information that comes in the form ...doi:10.4230/dagrep.8.2.64 dblp:journals/dagstuhl-reports/BonamiGLM18 fatcat:fn6llvricbevzjsm4teuf5xuha
 Fani Boukouvala and Marianthi G.Ierapetritou, Surrogate- Based Optimization of Expensive Flowsheet Modeling for Continuous Pharmaceutical Manufacturing, Journal of Pharmaceutical Innovation ...doi:10.18831/djmicro.org/2016011003 fatcat:lnwesmqlpba53krnjgwahwmkbu
Optimization using both models and input-output data Fani Boukouvala (Georgia Institute of Technology -Atlanta, US) License Creative Commons BY 3.0 Unported license © Fani Boukouvala Joint work of Fani ... Optimization using both models and input-output data Fani Boukouvala . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ...doi:10.4230/dagrep.8.2 fatcat:6kf77nt6j5g2jatriorn72fafm